Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

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Abstract

Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4 ⁺ and CD8 ⁺ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

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Most cited references 92

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NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes.

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Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.

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Author and article information

Journal

Journal ID (nlm-ta): Immune Netw

Journal ID (iso-abbrev): Immune Netw

Journal ID (publisher-id): IN

Title: Immune Network

Publisher: The Korean Association of Immunologists

ISSN (Print): 1598-2629

ISSN (Electronic): 2092-6685

Publication date (Print): February 2016

Publication date (Electronic): 25 February 2016

Volume: 16

Issue: 1

Pages: 33-43

Affiliations

[1 ]Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.

[2 ]Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.

Author notes

Corresponding Author. Je-Min Choi, Department of Life Science, College of Natural Sciences, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. Tel: 82-2-2220-4765; Fax: 82-2-2299-3495; jeminchoi@ 123456hanyang.ac.kr

^#These authors contributed equally to this work.

Article

DOI: 10.4110/in.2016.16.1.33

PMC ID: 4770098

PubMed ID: 26937230

SO-VID: aba9d9da-9927-4bd8-9a0d-10e4c0d99cc0

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 13 December 2015

Date revision received : 21 January 2016

Date accepted : 26 January 2016

Funding

Funded by: Korea Health Industry Development Institute, CrossRef http://dx.doi.org/10.13039/501100003710;

Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

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Abstract

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Annual Reviews HIV/AIDS: Public Health and Society

Most cited references 92

Function and activation of NF-kappa B in the immune system.

Taking dendritic cells into medicine.

In vivo protein transduction: delivery of a biologically active protein into the mouse.

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